Carbonic Anhydrase IX (CAIX) expression predicts for renal cell cancer (RCC) patient response and survival to IL-2 therapy

Abstract

4512 Background: RCC response to IL-2 Rx and patient (pt) survival have been correlated to histology including the presence of clear cell and alveolar and the absence of papillary and granular features (Upton et al Proc ASCO, 2003) and CAIX expression (Bui et al Clin Ca Res 2003;9:802). In an effort to confirm and expand these findings we undertook a nested case-control study within the Upton cohort. Methods: Paraffin-embedded tissue sections of RCC were immunostained with an Ab to CAIX and expression levels were correlated with pathology findings, clinical outcome and the Upton model relating them. The percentage of CAIX positive tumor cells was utilized to separate high (> 85%) vs low (≤ 85%) expressers. Results: Tissue specimens were obtained from 66 pts (51M, 15F). 27 of the selected pts (41%) had responded (10CR/17PR) to IL-2. 24 (36%), 31 (47%) and 11 (17%) were classified as good, intermediate, and poor prognosis according to the Upton model. 41 specimens (62%) had high CAIX expression. 21 of 27 (78%) responding pts had high CAIX expression compared to 20/39 (51%) non-responders (OR=3.3; p=0.04); a similar survival benefit was seen (p=0.04). Survival >5 yrs was seen only in high CAIX expressors. High CAIX staining was associated with better pathology prognosis, and when stratified by group, the ORs of CAIX expression were unequal across groups (p=0.08) . The stongest association was in the intermediate group where 9/9 responders has high CAIX expression vs.11/22 non-responders, suggesting a possible refinement of the Upton model. A resultant group with good pathology or intermediate pathology and high CAIX contained 26 of 27 (96%) responders compared to only 18/39 (46%) non-responders (OR=30; p<0.01). Survival benefit was also seen (p< 0.01). Conclusions: We conclude that CAIX expression is an important predictor of outcome in RCC pts receiving IL-2-based Rx and can enhance prognostic information obtained from pathology specimens. While this refinement to the pathology model requires validation, data suggest that IL-2 Rx might ultimately be reserved for pts with Upton model good pathology alone or intermediate pathology and high CAIX staining. No significant financial relationships to disclose.